Current use of oral contraceptives and the risk of first-ever ischemic stroke: A meta-analysis of observational studies

Objective: To evaluate the risk of first-ever ischemic stroke associated with current use of oral contraceptive pills (OCPs), and to describe how the risk was influenced by estrogen dose, progestin type, and study characteristics.

Methods: We obtained relevant articles published between 1970 and March 2014 by conducting a search of Pubmed, Embase and the Cochrane Library. Two investigators independently identified eligible studies based on selection criteria in a two-step method. The quality of studies was assessed with the Newcastle-Ottawa scale. Pooled odds ratios were calculated with a random-effects meta-analysis model.

Results: A total of 18 independent studies (3 cohort studies and 15 case-control studies) were identified. The overall summary odds ratio for first-ever ischemic stroke risk associated with current OCP use compared with noncurrent OCP use was 2.47 [95% confidence interval (CI), 2.04-2.99]. The risk of ischemic stroke among current OCP users decreased significantly with decreasing estrogen dose: OCPs of ≥50μg ethinyl estradiol (EE), 30-40 ug EE, 20 ug EE and progestin only pills implied odds ratios of 3.28 (95%CI, 2.49-4.32), 1.75 (95%CI, 1.61-1.89), 1.56 (95%CI, 1.36-1.79), and 0.99 (95%CI, 0.71-1.37), respectively. All four generations of progestin were associated with an elevated risk of ischemic stroke, and the risk of ischemic stroke among users of the fourth-generation progestins seemed to be slightly lower than those of other generations of progestins.

Conclusions: Data from observational studies suggest that current use of modern OCPs is associated with an increased risk of first-ever ischemic stroke. OCPs containing lower estrogen doses incline to contribute to a smaller elevated risk of ischemic stroke.